Advances in nanoscopic mechanobiological structure-property relationship in human bones for tailored fragility prevention

It is well documented that fragility fractures represent an enormous health, economic and psycho-social burden, leading to severe pain, loss of mobility, and even death. While clinical approaches focusing on macro down to micro-scale damage in bones are often ineffective to diagnose early fracture occurrence, nano-scale investigations are opening new frontiers for targeted fragility prevention. This review highlights a novel triad that merges advanced nano-imaging techniques, nano-mechanical characterization and finite element/molecular dynamics-based computational models to elucidate the structure-property relationship that leads to bone fractures. Techniques such as atomic force microscopy and high-resolution electron microscopy enable the evaluation of mechanobiological mechanisms and damage occurrence at the sub-micro scale, providing visualization of bone ultrastructure. Simultaneously, nanoindentation and micropillar compression offer precise measurements of mechanical properties, unraveling how bone responds to diverse forces. Pertaining computational tools, nano-scale modeling simulations explore the behavior of bone components under varying conditions, yielding crucial insights into fracture mechanisms. This holistic triad unveils interactions between mineralized collagen fibrils, cross-links, and bone structures, leading to targeted prevention and personalized treatment of bone fragility, by addressing their root causes at the nano-scale, potentially lowering their incidence and severity

Government control of agrarian field of economics in the conditions of global challenge and threats

Political, economic and social importance of agrarian problems in the Russian Federation has received extremely sharp sound associated with ensuring food security, import substitution of food which requires reasonable macroeconomic and financial government management, including the adaptation of modern measures of government regulation of rural development to the new economic conditions. In this regard, the economic science once again faces with the task of understanding and studying of the theoretical positions and methodological approaches to the development of a new agricultural policy, to the search of optimal forms and methods of government influence on the agricultural market, building a system of cooperation between government, business and the peasantry on the basis of maximal coordination of mechanisms of government regulation of the agrarian sector with the motivational structure of the rural population in terms of adaptation to modern agricultural methods and tools of influence. This article contains the argumentation of the provisions on the development of the system of government regulation of the agrarian sector of the Russian economy in the new economic conditions that will ensure import substitution, increase in the competitiveness of Russia in the global food market.peer-reviewe

Interplay between CCR7 and Notch1 axes promotes stemness in MMTV-PyMT mammary cancer cells

Background: Breast cancer is the major cause of cancer-related mortality in women. It is thought that quiescent stem-like cells within solid tumors are responsible for cancer maintenance, progression and eventual metastasis. We recently reported that the chemokine receptor CCR7, a multi-functional regulator of breast cancer, maintains the stem-like cell population. Methods: This study used a combination of molecular and cellular assays on primary mammary tumor cells from the MMTV-PyMT transgenic mouse with or without CCR7 to examine the signaling crosstalk between CCR7 and Notch pathways. Results: We show for the first time that CCR7 functionally intersects with the Notch signaling pathway to regulate mammary cancer stem-like cells. In this cell subpopulation, CCR7 stimulation activated the Notch signaling pathway, and deletion of CCR7 significantly reduced the levels of activated cleaved Notch1. Moreover, blocking Notch activity prevented specific ligand-induced signaling of CCR7 and augmentation of mammary cancer stem-like cell function. Conclusion: Crosstalk between CCR7 and Notch1 promotes stemness in mammary cancer cells and may ultimately potentiate mammary tumor progression. Therefore, dual targeting of both the CCR7 receptor and Notch1 signaling axes may be a potential therapeutic avenue to specifically inhibit the functions of breast cancer stem cells.Sarah T. Boyle, Krystyna A. Gieniec, Carly E. Gregor, Jessica W. Faulkner, Shaun R. McColl and Marina Kochetkov

The chemokine receptor CCR6 facilitates the onset of mammary neoplasia in the MMTV-PyMT mouse model via recruitment of tumor-promoting macrophages

BACKGROUND: The expression of the chemokine receptor CCR6 has been previously correlated with higher grades and stages of breast cancer and decreased relapse-free survival. Also, its cognate chemokine ligand CCL20 has been reported to induce proliferation of cultured human breast epithelial cells. METHODS: To establish if CCR6 plays a functional role in mammary tumorigenesis, a bigenic MMTV-PyMT CCR6-null mouse was generated and mammary tumor development was assessed. Levels of tumor-infiltrating immune cells within tumor-bearing mammary glands from MMTV-PyMT Ccr6 (WT) and Ccr6 (-/-) mice were also analyzed. RESULTS: Deletion of CCR6 delayed tumor onset, significantly reduced the extent of initial hyperplastic outgrowth, and decreased tumor incidence in PyMT transgenic mice. CCR6 was then shown to promote the recruitment of pro-tumorigenic macrophages to the tumor site, facilitating the onset of neoplasia. CONCLUSIONS: This study delineated for the first time a role for CCR6 in the development of breast cancer, and demonstrated a critical function for this receptor in maintaining the pro-tumorigenic cancer microenvironment.Sarah T. Boyle, Jessica W. Faulkner, Shaun R. McColl, and Marina Kochetkov

Economic tools for realization of methane production project on Kuzbass coal deposits

Environmental issues and, above all, issues related to the release of greenhouse gases into the atmosphere, such as coal bed methane, actualize the challenge of searching a variety of options for its disposal. The difference in the macroeconomic, industrial, geological and infrastructural features determine the need to choose the most cost-effective option for using of methane emitted from the coal deposits. Various economic ways to improve the profitability of production are viewed on the basis of the analysis of methane production project from Kuzbass coal deposits, Kemerovo region, Russia

The features of reproductive health in women with multiple sclerosis

Introduction. The incidence of multiple sclerosis (MS) is two times higher in women, and the debut of the disease falls on young reproductive age, which makes the problem urgent. Purpose: to assess the characteristics of the reproductive health of women with MS in different age periods. Material and methods. A prospective study was carried out in parallel groups and a case-control study of women of early and late reproductive age with a reliable diagnosis of MS. Results. During pregnancy, there was a significant decrease in the frequency of exacerbations of MS in comparison with the pre-gravity period; voluntary infertility and childlessness is registered in 21.3 % and 32 % of women, respectively. An increase in the concentration of follicle stimulating hormone (FSH) means an increase in the degree of disability on the Expanded Disability Status Scale (EDSS) and the duration of the disease. The decrease in the concentration of dehydroepiandrosterone sulfate (DHEA-S) corresponds to a higher degree of disability on the EDSS scale and the duration of the disease. Conclusion. Pregnancy has a protective effect on the clinical course of MS. Infertility in most cases is voluntary, but at the same time hypergonadotropic condition and hypoandrogenia are observed in women with MS already in the early reproductive age, which interferes with the steroid synthetic function of the ovaries and can cause impaired fertility

Energy efficiency, low-carbon energy production, and economic growth in CIS countries

The paper studies the peculiarities of energy efficiency increase in national economy and decrease of carbon dioxide emission for CIS countries. The conditions that allow achieving parameters of sustainable development are determined according to indexes of GDP energy intensity and carbon intensity. Focusing on the indexes of GDP energy intensity and carbon intensity dynamics as well as on carbon intensity of energy production, a real movement towards implementation of program conditions presented by international organizations is analyzed, namely, economic conversion to the model of sustainable development. The examples demonstrate both the presence of significant differences between 12 countries and the lack of fatality in these differences. At determining dependencies linear models are preferred to non-linear ones, with the explanation of reasons in each particular case. Attention to success of these countries may help to understand the advantages of conversion to the model of sustainable development and also it helps to decrease demands in terms of costs for this conversion

Cxcr4-ccr7 heterodimerization is a driver of breast cancer progression

Metastatic breast cancer has one of the highest mortality rates among women in western society. Chemokine receptors CXCR4 and CCR7 have been shown to be linked to the metastatic spread of breast cancer, however, their precise function and underlying molecular pathways leading to the acquisition of the pro-metastatic properties remain poorly understood. We demonstrate here that the CXCR4 and CCR7 receptor ligands, CXCL12 and CCL19, cooperatively bind and selectively elicit synergistic signalling responses in invasive breast cancer cell lines as well as primary mammary human tumour cells. Furthermore, for the first time, we have documented the presence of CXCR4-CCR7 heterodimers in advanced primary mammary mouse and human tumours where number of CXCR4-CCR7 complexes directly correlate with the severity of the disease. The functional significance of the CXCR4-CCR7 association was also demonstrated when their forced heterodimerization led to the acquisition of invasive phenotype in non-metastatic breast cancer cells. Taken together, our data establish the CXCR4-CCR7 receptor complex as a new functional unit, which is responsible for the acquisition of breast cancer cell metastatic phenotype and which may serve as a novel biomarker for invasive mammary tumours.Valentina Poltavets, Jessica W. Faulkner, Deepak Dhatrak, Robert J. Whitfield, Shaun R. McColl and Marina Kochetkov